Coley's Toxins - "Father of Immunotherapy"

The resolution of inflammation and cancer.
Juan Rodriguez-Vita, Toby Lawrence
Inflammation Biology Group, Centre d'Immunologie Marseile-Luminy, Parc Scientifique de Luminy Case 906, 13288 Marseille, France(1).

Inflammation has long been thought to contribute to the
development of cancer; however there is also clear
evidence that the immune system can recognize and
eliminate cancer cells. Current research suggests that
cancer-associated inflammation has a dual role in tumor
progression; inflammatory mediators promote the malignant
activity of cancer cells by acting as growth factors and
also stimulate angiogenesis, however, cancer-associated
inflammation is also linked with immune-suppression that
allows cancer cells to evade detection by the immune
system. In this review we will discuss the dual role of
inflammation in cancer and how endogenous
anti-inflammatory mechanisms may equally be important in
carcinogenesis.


BioDrugs. 2009 ;23 (6):361-75 19894778
CpG Oligodeoxyneucleotides as TLR9 Agonists: Therapeutic Applications in Cancer.
Yanal M Murad, Timothy M Clay
Duke University Medical Center, Department of Surgery, Program in Molecular Therapeutics, Comprehensive Cancer Center, Durham, North Carolina, USA.

Toll-like receptors (TLRs) are part of the innate immune
system, and they belong to the pattern recognition
receptors (PRR) family. The PRR family is designed to
recognize and bind conserved pathogen-associated molecular
patterns, which are not generated by the host and are
restricted and essential to micro-organisms. TLR9, which
recognizes unmethylated CpG (cytosine guanosine
dinucleotide), is a very promising target for therapeutic
activation. Stimulation of TLR9 activates human
plasmacytoid dendritic cells and B cells, and results in
potent T helper-1 (T(h)1)-type immune responses and
antitumor responses in mouse tumor models and in patients.
Several pharmaceutical companies, such as Pfizer, Idera,
and Dynavax, are developing CpG oligodeoxynucleotides
(ODNs) for the treatment of cancer, along with other
conditions, such as infections and allergy. CpG ODNs have
shown promising results as vaccine adjuvants and in
combination with cancer immunotherapy. Several TLR9
agonists are being developed and have entered clinical
trials to evaluate their safety and efficacy for the
treatment of several hematopoietic and solid tumors. In
this review, we discuss the use of CpG ODNs in several
phase I and II clinical trials for the treatment of NHL,
renal cell carcinoma, melanoma, and non-small cell lung
cancer, either alone or in combination with other agents.

Immunol Res. 2009 Sep 15;: 19756410
Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia.
Adrienne Peer, Melissa Grimm, Evan Zynda, Elizabeth Repasky
Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.

There is increasing documentation of significant survival
benefits achieved in cancer patients treated with
hyperthermia in combination with radiation and/or
chemotherapy. Most evidence collected regarding the
mechanisms by which hyperthermia positively influences
tumor control has centered on in vitro data showing the
ability of heat shock temperatures (usually above 42
degrees C) to result in radio- or chemosensitization.
However, these high temperatures are difficult to achieve
in vivo, and new thermometry data in patients reveal that
much of the tumor and surrounding region is only heated to
40-41 degrees C or less as a result of vascular drainage
from the target zone of the heated tumor. Thus, there is
now a growing appreciation of a role for mild hyperthermia
in the stimulation of various arms of the immune system in
contributing to long term protection from tumor growth.
Indeed, a review of recent literature suggests the
existence of an array of thermally sensitive functions
which may exist naturally to help the organism to
establish a new "set point" of immune responsiveness
during fever. This review summarizes recent literature
identifying complex effects of temperature on immune cells
and potential cellular mechanisms by which increased
temperature may enhance immune surveillance.


Lessons from Coley's Toxin.
Kangla Tsung, Jeffrey A Norton
Department of Surgery, Stanford University School of Medicine, Room H3591, 300 Pasteur Drive, Stanford, CA 94025, USA.

The active molecule in Coley's Toxin is not tumor necrosis
factor (TNF) or endotoxin (LPS), but interleukin-12
(IL-12). IL-12 holds the key to improved anti-tumor immuns
response.



Iowa Orthop J. 2006 ;26 :154-8 16789469
The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas.
Edward F McCarthy
Department of Pathology and Orthopaedic Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. mccarthy@jhmi.edu

In 1891, William B. Coley injected streptococcal organisms
into a patient with inoperable cancer. He thought that the
infection he produced would have the side effect of
shrinking the malignant tumor. He was successful, and this
was one of the first examples of immunotherapy. Over the
next forty years, as head of the Bone Tumor Service at
Memorial Hospital in New York, Coley injected more than
1000 cancer patients with bacteria or bacterial products.
These products became known as Coley's Toxins. He and
other doctors who used them reported excellent results,
especially in bone and soft-tissue sarcomas. Despite his
reported good results, Coley's Toxins came under a great
deal of criticism because many doctors did not believe his
results. This criticism, along with the development of
radiation therapy and chemotherapy, caused Coley's Toxins
to gradually disappear from use. However, the modern
science of immunology has shown that Coley's principles
were correct and that some cancers are sensitive to an
enhanced immune system. Because research is very active in
this field, William B. Coley, a bone sarcoma surgeon,
deserves the title "Father of Immunotherapy".